Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002046988 | SCV002108871 | uncertain significance | Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function | 2022-07-21 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1349527). Disruption of this splice site has been observed in individual(s) with primary immunodeficiency (PMID: 32888943). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 6 of the STAT3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in STAT3 cause disease. |
| 3billion | RCV003314023 | SCV004013833 | pathogenic | STAT3-related early-onset multisystem autoimmune disease | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. It is a splice variant located at canonical splice site predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported to be associated with STAT3-related disorder (PMID: 32888943). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |